Non-Coding RNAs in Pancreatic Cancer Diagnostics and Therapy: Focus on lncRNAs, circRNAs, and piRNAs

Abstract

Pancreatic cancer is an aggressive malignance with high mortality. The lack of early diagnosis and effective therapy contributes to the high mortality of this deadly disease. For a long time being, the alterations in coding RNAs have been considered as major targets for diagnosis and treatment of pancreatic cancer. However, with the advances in high-throughput next generation of sequencing more alterations in non-coding RNAs (ncRNAs) have been discovered in different cancers. Further mechanistic studies have demonstrated that ncRNAs such as long noncoding RNAs (lncRNA), circular RNAs (circRNA) and piwi-interacting RNA (piRNA) play vital roles in the regulation of tumorigenesis, tumor progression and prognosis. In recent years, increasing studies have focused on the roles of ncRNAs in the development and progression of pancreatic cancer. Novel findings have demonstrated that lncRNA, circRNA, and piRNA are critically involved in the regulation of gene expression and cellular signal transduction in pancreatic cancer. In this review, we summarize the current knowledge of roles of lncRNA, circRNA, and piRNA in the diagnosis and prognosis of pancreatic cancer, and molecular mechanisms underlying the regulation of these ncRNAs and related signaling in pancreatic cancer therapy. The information provided here will help to find new strategies for better treatment of pancreatic cancer.

Molecular and metabolic regulation of immunosuppression in metastatic pancreatic ductal adenocarcinoma

“…Functionally, the miRs bind to the mRNA transcripts and modulate protein translation and their function, while lncRNAs support small RNAs such as miRs by facilitating their binding to the targets and regulate their functions [ 176 ]. Recent studies have highlighted the pathophysiological and therapeutic significance of ncRNA in PDAC, highlighting their role in disease progression, metastasis, and therapy resistance [ 177 – 180 ], and their utility as biomarkers and therapeutic targets [ 181 – 183 ]. Interestingly, ncRNAs have been shown to regulate PDAC pathobiology via both tumor-promoting and restraining functions [ 178 , 184 ].…”

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

“…They can activate or inhibit epigenetic-related proteins by binding to them, control the generation of miRNAs, and promote or inhibit gene transcription by base-pairing and by recruiting transcription factors [ 84 ]. LncRNAs are encoded within introns or intergenic regions of genes, with sequences either sense or antisense of the respective genes [ 59 ]. The number of lncRNA loci in the human genome has recently been estimated around 96,000 [ 85 ].…”

“…Since they are also present cell-free in biological fluids, lncRNAs are potential biomarkers for screening, diagnostics, prognostics or disease monitoring [ 88 ]. In PC, important differentially expressed lncRNAs are HOTAIR , HOTTIP , H19 , MALAT1 , PVT1 , GAS5 , and MEG3 , amongst others, as reviewed by [ 59 ].…”

“…Like miRNAs and lncRNAs, they have important functions in the posttranscriptional regulation of gene expression, e.g., by competing with mRNAs, interacting with RNA binding proteins, and sponging miRNAs. They too can act in oncogenic or tumor suppressive ways [ 59 , 90 ]. CircRNAs are differentially expressed in PC, more stable due to their circular shape compared to other ncRNAs, and tissue-specific, which makes them ideal biomarkers and potential therapeutic targets [ 84 ].…”

“…Likewise, PIWI-interacting RNAs (piRNAs) have been detected differentially expressed in PC. They too have important regulatory functions, being involved in the initiation, progression and metastasis of cancer [ 59 , 84 , 91 ].…”